Effects of resistance exercise training on mass, strength, and turnover of bone in growing rats

To determine the effects of resistance exercise on mass, strength and local turnover of bone, 50 Sprague Dawley rats, 8 weeks of age, were assigned to five groups: a baseline control and two groups of sedentary and exercising rats. The trunk of the rats was kept upright during electrically stimulated jumping exercise for 1 h every other day. In 4 weeks, the trabecular mineralizing surface per bone surface (MS/BS), bone formation rate per bone surface (BFR/BS) and the compression load of the lumbar body increased and the number of osteoclasts decreased, but bone mineral density (BMD) and structure did not increase. In the mid femur, the cross-sectional area, the cortical bone area, the moment of inertia, the periosteal MS/BS, BFR/BS and the bending load increased in the exercise group. In 8 weeks, the increases in BMD, structure and load values were significant in both the lumbar and mid femur. At both 4 and 8 weeks, the MS/BS for the endocortical surface of mid femur were not increased and mineral apposition rate (MAR) remained reduced. These results show that jumping exercise increases the mass and strength of the lumbar vertebrae and mid femur by stimulating bone formation and accelerates cortical drift by both increasing periosteal bone formation and reducing the endocortical MAR. Accepted: 1 February 2000     

A comparison of resistance and aerobic training for mass, strength and turnover of bone in growing rats

To determine the effects of resistance versus aerobic exercise on the mass, strength and turnover of bone, thirty Sprague Dawley rats (4 weeks of age) were assigned to one of three experimental groups: sedentary, running or jumping. In the jumping group, the trunk was kept upright during electrically stimulated jumping exercise for 1 h every other day. The running rats ran at speeds of 24 m/min for 1 h every other day. After 4 weeks, the jumping rats exhibited increases in the mass and strength of the lumbar vertebrae and of the mid-diaphysis of the femur (mid-femur), and increases in the cross-sectional morphology of these bones: the trabecular bone volume per bone surface, the trabecular thickness, the trabecular bone formation rate per bone surface (BFR/BS). In addition, they exhibited reduced trabecular separation and the area of osteoclast surface per bone surface. The running and sedentary rats showed no such changes. With regard to the mid-femur, in both the jumping and running rats the periosteal BFR/BS was increased. However, only the jumping rats showed a reduction in the BFR/BS at the endocortical surface. These results suggest that resistance exercise accelerates cortical drift and increases the bone mass and strength by stimulating bone formation more efficiently than does aerobic exercise. Accepted: 9 August 2000     

Osteoclast abnormalities in idiopathic osteopetrosis

Summary In order to investigate skeletal abnormalities in a case of idiopathic osteopetrosis, a bone biopsy was taken from the anterior iliac crest and prepared for ultrastructural and histochemical study. There was a drastic reduction in osteoclastic bone resorption. The ruffle border and sealing zone, which are the osteoclast cell surface markers of bone resorption, were absent. The cells were highly vacuolated, and the vacuoles contained large amounts of a residual organic material which reacted strongly with acid phosphatase. Acid phosphatase activity was never found outside the cell, and in particular, not at the brine-cell interface.This suggests that the defect in bone resorption is caused by cell membrane abnormalities and the lack of ruffle border formation, rather than the inability of the lysosomal enzymes to digest the bone matrix.     

Endometrial adenosquamous carcinoma with osteoclast-like giant cells: immunohistochemistry and histogenesis

Primary extraskeletal epithelial neoplasms containing osteoclast-like giant cells (OGCs) are rare. We herein describe a case of adenosquamous carcinoma that developed in the endometrium together with non-neoplastic OGCs. The patient was a 72-year-old woman who underwent radical hysterectomy with salpingo-oophorectomy and lymph node dissection after being diagnosed with uterine cancer. Histologically, the tumor was found to be an adenosquamous carcinoma containing a large number of OGCs and mononuclear cells (MNCs) that had infiltrated into the stroma. Immunohistochemically, the OGCs and MNCs stained strongly positive for KP-1 and alpha-1-antichymotrypsin, and negative for the epithelial markers epithelial membrane antigen (EMA) and cytokeratins. These findings suggest that the OGCs and MNCs in this patient's tumor originated from monocytes/histiocytes, and most likely developed as part of the stromal reaction to the neoplasm.     

Osteoclast formation from mouse bone marrow cells on micro/nano-scale patterned surfaces

ObjectivesOsteoclasts can sense the surface topography of materials. However, it is difficult to identify the structural factors that affect osteoclast formation and its function. Furthermore, we hypothesized that the type of osteoclast precursor cells also affects osteoclastogenesis in the materials. In this study, we investigated the effects of defined micro/nanoscale patterns on osteoclastogenesis from bone marrow cells (BMCs).MethodsVarious cyclo-olefin polymer (COP) patterns were prepared using nanoimprinting. The effects of shape, size, and height of the patterns, and the wettability of the patterned surfaces on osteoclastogenesis from BMCs were evaluated in vitro.ResultsOsteoclast formation was promoted on pillars (diameter, 1 μm or 500 nm; height, 500 nm). Notably, osteoclastogenesis from BMCs was better promoted on hydrophobic pillars than on hydrophilic pillars. In contrast, decreased osteoclast formation was observed on the nanopillars (diameter, 100 nm; height, 200 nm).ConclusionsWe demonstrated the promotion of osteoclast formation from BMCs on hydrophobic pillars with diameters of 1 μm and 500 nm. Some cellular behaviors in the patterns were dependent on the type of osteoclast precursor cells. The designed patterns are useful for designing the surface of dental implants or bone replacement materials with a controllable balance between osteoblast and osteoclast activities.     

A case of pulmonary adenocarcinoma harboring osteoclast‐like giant cells: Its evaluation by immunohistochemical and genetic analyses

Tumors harboring osteoclast‐like giant cells (OGCs) at extraosseous site are extremely rare. These rare tumors have been detected most frequently in the pancreas and few pulmonary tumors harboring OGCs have been previously reported. In addition, the genetic profiles of these tumors have remained virtually unknown. Therefore, we report a case of pulmonary adenocarcinoma harboring OGCs in which k‐ras mutation and immunohistochemical study of proteins associated with OGCs were examined. The case was a 70‐year‐old man, who demonstrated a pulmonary mass associated with unusual radiological features. Histopathologically, three different cell types, mucinous adenocarcinoma cell, OGC and mononuclear cell were detected. OGCs were immunohistochemically negative for epithelial markers and positive for histiocytic markers but mononuclear cells were immunopositive for epithelial markers. In addition, both mononuclear and adenocarcinoma cells had the same k‐ras mutation profiles and mononuclear cells were immunohistochemically positive for macrophage colony‐stimulating factor (M‐CSF), one of the factors associated with OGC differentiation. Therefore, mononuclear cells were considered to be derived from neoplastic epithelium and OGCs could represent non‐neoplastic cells. In addition, M‐CSF locally produced could promote the differentiation of OGCs.     

唑来膦酸抑制RAW264.7细胞系分化的最佳浓度体外实验

目的观察唑来膦酸盐对RAW264.7细胞系毒性作用的浓度范围和抑制RAW264.7分化为破骨细胞的最佳实验浓度。 方法以小鼠前破骨细胞系RAW264.7为研究对象,应用MTT法检测唑来膦酸盐对小鼠前破骨细胞系RAW264.7的毒性作用范围。使用TARP染色法观察不同浓度的唑来膦酸盐作用下破骨细胞的生成数目。 结果体外培养24 h后,酶联免疫反应吸光度结果显示,10^-3 mol/L（0.511±0.920）,10^-4 mol/L（0.615±0.577）唑来膦酸对小鼠前破骨细胞系RAW264.7增殖有毒性作用,与空白对照组（0.789±0.061）相比,差异有统计学意义（F=5.880,P<0.01）。TRAP染色破骨细胞计数结果显示：10^-5 mol/L（8.333±0.817）、10^-6 mol/L（10.400±1.817）、10^-7 mol/L（11.250±2.750）及10^-8 mol/L（11.143±1.864）唑来膦酸盐实验组破骨细胞数与空白对照组破骨细胞数（13.833±2.483）相比,差异具有统计学意义（F=27.972,P<0.05）,且呈浓度依赖性,当唑来膦酸盐浓度为10^-5 mol/L时,抑制效果最明显（P<0.01）。 结论唑来膦酸盐抑制RAW264.7细胞系分化为破骨细胞的最佳体外实验浓度为10^-5 mol/L。     

白细胞介素-24通过Jak-Stat通路对破骨细胞影响的实验研究

目的:研究白细胞介素-24(interleukin-24,IL-24)在体外通过Jak-Stat信号通路对单核巨噬细胞向破骨细胞分化的影响。方法:使用增强型绿色荧光蛋白(EGFP)确定最佳感染复数(MOI);使用ELISA检测培养基中IL-24的含量;采用Real-time PCR方法检测RAW264.7细胞中Jak-Stat信号通路相关基因Jak1、Jak2、Jak3、Stat1、Stat2、Stat3及其向破骨细胞分化过程中相关基因NFATc1、CTSK、MMP9 mRNA的表达。结果:MOI=600为最佳转染效率;转染组IL-24含量显著高于未转染组(P＜0.01);在RANKL诱导条件下转染IL-24的RAW264.7细胞与未转染组相比Jak2、Stat3 mRNA的表达增加(P＜0.05),在RANKL诱导条件下转染IL-24的RAW264.7细胞加入信号通路抑制剂后与未加入抑制剂组相比,向破骨细胞分化过程中相关基因NFATc1、CTSK、MMP9 mRNA的表达降低(P＜0.05)。结论:IL-24通过Jak-Stat信号通路调控破骨细胞的分化及功能。     

无机骨材料对上颌窦提升术后骨再生的影响

目的：研究兔上颌窦提升术后扩增区域内新生骨的改建过程和破骨细胞的分布情况,探讨无机骨颗粒对上颌窦提升术后骨再生的影响。方法：对8只日本大耳白兔施行上颌窦提升术。实验组扩增区植入无机骨颗粒,对照组仅使血凝块充满扩增区,不填充移植材料。结果：术后4周,对照组扩增区近窦黏膜处的新生骨表面可见大量破骨细胞。组织形态测量学分析表明,术后4周至8周实验组窦底提升高度显著大于对照组;术后8周时实验组新生骨面积较对照组明显增加。结论：上颌窦内存在的空气压力可导致上颌窦提升术后新生骨发生吸收。在上颌窦提升术中使用无机骨填充材料可抵抗上颌窦内的空气压力,并具有良好的骨重建效果。     

钛颗粒负荷对成骨细胞释放细胞因子的影响

假体周围的溶骨性因子是造成无菌性松动的主要原因之一。前期的研究表明,磨损颗粒抑制成骨细胞分化和矿化能力,为探索不同直径的磨损颗粒对成骨细胞释放细胞因子的影响,我们采用双夹心抗体ELISA、RT-PCR法分析3种直径钛颗粒对兔成骨细胞表达IL-6I、L-10和破骨细胞分化因子(ODF)的影响。结果显示:0.9μm钛颗粒刺激成骨细胞产生大量促骨吸收因子(IL-6、ODF)的同时快速而短暂地释放抑骨吸收因子(IL-10);2.7μm和6.9μm钛颗粒,尤其是后者主要是刺激成骨细胞缓慢而强烈地产生促骨吸收因子。提示:磨屑颗粒作用成骨细胞的生物学反应是双相的,且反应程度因颗粒大小和作用时间的不同而又有所不同。可见如何抑制假体周围溶骨性因子的产生以及人工材料的优化选择是提高人工假体寿命的关键。